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Search Results for all work with filters:

  • 2017
  • biomedicin

Work 1-10 of 1260

Sorted by relevance
  1. 1
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Article

Gene methylation biomarkers in sputum as a classifier for lung cancer risk

by Shuguang Leng; Guodong Wu; Donna M. Klinge; Cynthia L. Thomas; Elia Casas; Maria A. Picchi; Christine A. Stidley; Sandra J. Lee; Seena Aisner; Jill M. Siegfried; Suresh Ramalingam; Fadlo Khuri; Daniel D. Karp; Steven A. Belinsky

2017

Subjects
  • Health Sciences, Oncology
  • Health Sciences, Pharmacology
  • Biology, Genetics
  • View Abstract

Abstract:Close

CT screening for lung cancer reduces mortality, but will cost Medicare ~2 billion dollars due in part to high false positive rates. Molecular biomarkers could augment current risk stratification used to select smokers for screening. Gene methylation in sputum reflects lung field cancerization that remains in lung cancer patients postresection. This population was used in conjunction with cancer-free smokers to evaluate classification accuracy of a validated eight-gene methylation panel in sputum for cancer risk. Sputum from resected lung cancer patients (n=487) and smokers from Lovelace (n=1380) and PLuSS (n=718) cohorts was studied for methylation of an 8-gene panel. Area under a receiver operating characteristic curve was calculated to assess the prediction performance in logistic regressions with different sets of variables. The prevalence for methylation of all genes was significantly increased in the ECOG-ACRIN patients compared to cancer-free smokers as evident by elevated odds ratios that ranged from 1.6 to 8.9. The gene methylation panel showed lung cancer prediction accuracy of 82-86% and with addition of clinical variables improved to 87-90%. With sensitivity at 95%, specificity increased from 25% to 54% comparing clinical variables alone to their inclusion with methylation. The addition of methylation biomarkers to clinical variables would reduce false positive screens by ruling out onethird of smokers eligible for CT screening and could increase cancer detection rates through expanding risk assessment criteria.

Article

Protocol for the Emory University African American Vaginal, oral, and gut microbiome in pregnancy cohort study (vol 17, 161, 2017)

by Timothy Read; Anne Dunlop; Jennifer Mulle; Elizabeth Corwin; Carol Hogue; Bradley Pearce; Cherie Hill

2017

  • View Abstract

Abstract:Close

© 2017 The Author(s). Following publication of the original article [1], the authors pointed out that the Methods included one step that is no longer necessary but which was inadvertently carried over from an earlier protocol.

Article

Use of troponin assay 99th percentile as the decision level for myocardial infarction diagnosis

by Akshay Bagai; Karen P. Alexander; Jeffrey S. Berger; Roxy Senior; Chakkanalil Sajeev; Radoslaw Pracon; Kreton Mavromatis; Jose Luis Lopez-Sendon; Gilbert Gosselin; Ariel Diaz; Gian Perna; Jarozlaw Drozdz; Dennis Humen; Birute Petrauskiene; Asim N. Cheema; Denis Phaneuf; Subhash Banerjee; Todd D. Miller; Sasko Kedev; Herwig Schuchlenz; Gregg W. Stone; Shaun G. Goodman; Kenneth W. Mahaffey; Allan S. Jaffe; Yves D. Rosenberg; Sripal Bangalore; L. Kristin Newby; David J. Maron; Judith S. Hochman; Bernard R. Chaitman

2017

Subjects
  • Health Sciences, Medicine and Surgery
  • File Download
  • View Abstract

Abstract:Close

Background The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known. Methods We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute–sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained. Results Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the troponin concentration used locally to diagnose myocardial infarction to the assay manufacturer–determined 99th percentile URL was <1 at 19 (6.6%) laboratories, equal to 1 at 91 (31.6%) laboratories, >1 to ≤5 at 101 (35.1%) laboratories, >5 to ≤10 at 34 (11.8%) laboratories, and >10 at 43 (14.9%) laboratories. The variability in troponin decision level for myocardial infarction relative to the assay 99th percentile URL was present for laboratories in and outside of the United States, as well as for high- and standard-sensitivity assays. Conclusions There is substantial hospital-level variation in the troponin threshold used to diagnose myocardial infarction; only one-third of hospital laboratories currently follow the Universal Definition of Myocardial Infarction consensus recommendation for use of troponin concentration at the 99th percentile of a normal reference population as the decision level to diagnose myocardial infarction. This variability across laboratories has important implications for both the diagnosis of myocardial infarction in clinical practice as well as adjudication of myocardial infarction in clinical trials.

Article

Maternal exposure to childhood maltreatment and risk of stillbirth

by Alexa A. Freedman; Alison L. Cammack; Jeff R. Temple; Robert M. Silver; Donald J. Dudley; Barbara Stoll; Michael W. Varner; George R. Saade; Deborah Conway; Robert L. Goldenberg; Carol J Hogue

2017

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Obstetrics and Gynecology
  • File Download
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Purpose: To determine the association between maternal exposure to childhood maltreatment (CM) and risk of stillbirth (fetal death at or after 20 weeks' gestation). Methods: Population-based case-control study from the Stillbirth Collaborative Research Network (SCRN) conducted in 2006-2008, and the follow-up study, SCRN-Outcomes after Study Index Stillbirth (SCRN-OASIS), conducted in 2009 in the United States. Cases (n = 133) included women who experienced a stillbirth, excluding stillbirths attributed to genetic/structural or umbilical cord abnormalities and intrapartum stillbirths. Controls (n = 500) included women delivering a healthy term live birth (excluding births less than 37 weeks gestation, neonatal intensive care unit admission, or death). CM exposure was measured using the Childhood Trauma Questionnaire, administered during the SCRN-OASIS study. Dichotomized scores for five subscales of CM (physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse) and an overall measure of CM exposure were analyzed using logistic regression. Results: Generally, there was no association between CM and stillbirth, except for the emotional neglect subscale (OR: 1.93; 95% CI: 1.17, 3.19). Conclusions: Childhood neglect is understudied in comparison to abuse and should be included in the future studies of associations between CM and pregnancy outcomes, including stillbirth.

Article

Chronic PM2.5 exposure and risk of infant bronchiolitis and otitis media clinical encounters

by Mariam S. Girguis; Matthew Strickland; Xuefei Hu; Yang Liu; Howard Chang; Candice Belanoff; Scott Bartell; Veronica M. Vieira

2017

Subjects
  • Health Sciences, Public Health
  • Health Sciences, Epidemiology
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Chronic particulate matter less than 2.5 μm in diameter (PM2.5) exposure can leave infants more susceptible to illness. Our objective is to estimate associations of the chronic PM2.5exposure with infant bronchiolitis and otitis media (OM) clinical encounters. We obtained all first time bronchiolitis (n = 18,029) and OM (n = 40,042) clinical encounters among children less than 12 and 36 months of age, respectively, diagnosed from 2001 to 2009 and two controls per case matched on birthdate and gestational age from the Pregnancy to Early Life Longitudinal data linkage system in Massachusetts. We applied conditional logistic regression to estimate odds ratios (OR) and confidence intervals (CI) per 2-μg/m3increase in lifetime average satellite based PM2.5exposure.Effect modification was assessed by age, gestational age, frequency of clinical encounter, and income. We examined associations between residential distance to roadways, traffic density, and infant bronchiolitis and OM risk. PM2.5was not associated with infant bronchiolitis (OR = 1.02, 95% CI = 1.00, 1.04) and inversely associated with OM (OR = 0.97, 95% CI = 0.95, 0.99). There was no evidence of effect modification. Compared to infants living near low traffic density, infants residing in high traffic density had elevated risk of bronchiolitis (OR = 1.23, 95% CI = 1.14, 1.31) but not OM (OR = 0.98, 95% CI = 0.93, 1.02) clinical encounter. We did not find strong evidence to support an association between early-life long-term PM2.5exposure and infant bronchiolitis or OM. Bronchiolitis risk was increased among infants living near high traffic density.

Article

Population Pharmacokinetic Analysis of Ixazomib, an Oral Proteasome Inhibitor, Including Data from the Phase III TOURMALINE-MM1 Study to Inform Labelling

by Neeraj Gupta; Paul M. Diderichsen; Michael J. Hanley; Deborah Berg; Helgi van de Velde; R. Harvey; Karthik Venkatakrishnan

2017

Subjects
  • Health Sciences, Pharmacy
  • Health Sciences, Oncology
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Ixazomib is an oral proteasome inhibitor, approved in USA, Canada, Australia and Europe in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. We report a population pharmacokinetic model-based analysis for ixazomib that was pivotal in describing the clinical pharmacokinetics of ixazomib, to inform product labelling. Plasma concentration–time data were collected from 755 patients who received oral or intravenous ixazomib in once- or twice-weekly schedules in ten trials, including the global phase III TOURMALINE-MM1 study. Data were analysed using nonlinear mixed-effects modelling (NONMEM software version 7.2, ICON Development Solutions, Hanover, MD, USA). Ixazomib plasma concentrations from intravenous and oral studies were described by a three-compartment model with linear distribution and elimination kinetics, including first-order linear absorption with a lag time describing the oral dose data. Body surface area on the volume of the second peripheral compartment was the only covariate included in the final model. None of the additional covariates tested including body surface area (1.2–2.7 m 2 ), sex, age (23–91 years), race, mild/moderate renal impairment and mild hepatic impairment were found to impact systemic clearance, suggesting that no dose adjustment is required based on these covariates. The geometric mean terminal disposition phase half-life was 9.5 days, steady-state volume of distribution was 543 L and systemic clearance was 1.86 L/h. The absolute bioavailability of an oral dose was estimated to be 58%.

Article

Fetal death certificate data quality: a tale of two US counties

by Lauren Christiansen-Lindquist; Carol J Hogue; Robert M. Silver; Corette B. Parker; Donald J. Dudley; Matthew A. Koch; Uma M. Reddy; George R. Saade; Robert L. Goldenberg

2017

Subjects
  • Health Sciences, Public Health
  • Health Sciences, Medicine and Surgery
  • Health Sciences, Obstetrics and Gynecology
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Purpose: Describe the relative frequency and joint effect of missing and misreported fetal death certificate (FDC) data and identify variations by key characteristics. Methods: Stillbirths were prospectively identified during 2006-2008 for a multisite population-based case-control study. For this study, eligible mothers of stillbirths were not incarcerated residents of DeKalb County, Georgia, or Salt Lake County, Utah, aged ≥13 years, with an identifiable FDC. We identified the frequency of missing and misreported (any departure from the study value) FDC data by county, race/ethnicity, gestational age, and whether the stillbirth was antepartum or intrapartum. Results: Data quality varied by item and was highest in Salt Lake County. Reporting was generally not associated with maternal or delivery characteristics. Reasons for poor data quality varied by item in DeKalb County: some items were frequently missing and misreported; however, others were of poor quality due to either missing or misreported data. Conclusions: FDC data suffer from missing and inaccurate data, with variations by item and county. Salt Lake County data illustrate that high quality reporting is attainable. The overall quality of reporting must be improved to support consequential epidemiologic analyses for stillbirth, and improvement efforts should be tailored to the needs of each jurisdiction.

Article

Facial Curvature Detects and Explicates Ethnic Differences in Effects of Prenatal Alcohol Exposure

by Michael Suttie; Leah Wetherill; Sandra W. Jacobson; Joseph L. Jacobson; H. Eugene Hoyme; Elizabeth R. Sowell; Claire Coles; Jeffrey R. Wozniak; Edward P. Riley; Kenneth L. Jones; Tatiana Foroud; Peter Hammond

2017

Subjects
  • Health Sciences, Obstetrics and Gynecology
  • Psychology, General
  • Health Sciences, Medicine and Surgery
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Background: Our objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer-based tools for screening facial form. Methods: All 415 individuals considered were evaluated by expert dysmorphologists and categorized as (i) healthy control (HC), (ii) fetal alcohol syndrome (FAS), or (iii) heavily prenatally alcohol exposed (HE) but not clinically diagnosable as FAS; 3D facial photographs were used to build models of facial form to support discrimination studies. Surface curvature-based delineations of facial form were introduced. Results: (i) Facial growth in FAS, HE, and control subgroups is similar in both cohorts. (ii) Cohort consistency of agreement between clinical diagnosis and HC-FAS facial form classification is lower for midline facial regions and higher for nonmidline regions. (iii) Specific HC-FAS differences within and between the cohorts include: for HC, a smoother philtrum in Cape Coloured individuals; for FAS, a smoother philtrum in Caucasians; for control-FAS philtrum difference, greater homogeneity in Caucasians; for control-FAS face difference, greater homogeneity in Cape Coloured individuals. (iv) Curvature changes in facial profile induced by prenatal alcohol exposure are more homogeneous and greater in Cape Coloureds than in Caucasians. (v) The Caucasian HE subset divides into clusters with control-like and FAS-like facial dysmorphism. The Cape Coloured HE subset is similarly divided for nonmidline facial regions but not clearly for midline structures. (vi) The Cape Coloured HE subset with control-like facial dysmorphism shows orbital hypertelorism. Conclusions: Facial curvature assists the recognition of the effects of prenatal alcohol exposure and helps explain why different facial regions result in inconsistent control-FAS discrimination rates in disparate ethnic groups. Heavy prenatal alcohol exposure can give rise to orbital hypertelorism, supporting a long-standing suggestion that prenatal alcohol exposure at a particular time causes increased separation of the brain hemispheres with a concomitant increase in orbital separation.

Article

Association of vitamin D intake and serum levels with fertility: results from the Lifestyle and Fertility Study

by June L. Fung; Terry Hartman; Rosemary L. Schleicher; Marlene B. Goldman

2017

Subjects
  • Health Sciences, Obstetrics and Gynecology
  • Health Sciences, Epidemiology
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Article

An Aggregate Biomarker Risk Score Predicts High Risk of Near-Term Myocardial Infarction and Death: Findings From BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes)

by Nima Ghasemzadeh; Maria M. Brooks; Helen Vlachos; Regina Hardison; Sergey Sikora; Laurence Sperling; Arshed Quyyumi; Stephen E. Epstein

2017

Subjects
  • Health Sciences, Public Health
  • Health Sciences, General
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Background-In a previous study, we found that a biomarker risk score (BRS) comprised of C-reactive protein, fibrin-degradation products, and heat shock protein-70 predicts risk of myocardial infarction and death in coronary artery disease patients. We sought to: (1) validate the BRS in the independent BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) cohort, (2) investigate whether 1 year of intensive medical therapy is associated with improved BRS, and (3) elucidate whether an altered BRS parallels altered risk. Methods and Results-Two thousand thirty-two subjects with coronary artery disease were followed for 5.3±1.1 years for cardiovascular events. Biomarkers were measured at baseline and retested in 1304 subjects at 1 year. BRS was determined as the biomarker number above previously defined cut-off values (C-reactive protein > 3 mg/L, heat shock protein-70 > 0.313 ng/mL, and fibrin-degradation products > 1 lg/mL). After adjustment for covariates, those with a BRS of 3 had a 4-fold increased risk of allcause death and a 6.8-fold increased risk of cardiac death compared with those with a BRS of 0 (95% CI, 2.9-16.0; P < 0.0001). All individual biomarkers decreased by 1 year, with ≈80% of patients decreasing their BRS. BRS recalibrated at 1 year also predicted risk. Those with 1-year BRS of 2 to 3 had a 4-year mortality rate of 21.1% versus 7.4% for those with BRS of 0 to 1 (P < 0.0001). Conclusions-Our results validate the ability of the BRS to identify coronary artery disease patients at very high near-term risk of myocardial infarction/death. After 1 year of intensive medical therapy, the BRS decreased significantly, and the reclassified BRS continued to track with risk. Our results suggest that repeated BRS measurements might be used to assess risk and recalibrate therapy.
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